Gallic acid attenuates torsion/detorsion-induced testicular injury in rats through suppressing of HMGB1/NF-κB axis and endoplasmic reticulum stress.

It was aimed to evaluate whether gallic acid (GA) have a beneficial effect in the testicular ischemia/reperfusion injury (IRI) model in rats for the first time. Testicular malondialdehyde, 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, catalase, high mobility group box 1 protein, nuclear factor kappa B, tumor necrosis factoralpha, interleukin-6, myeloperoxidase, 78-kDa glucose-regulated protein, activating transcription factor 6, CCAAT-enhancer-binding protein homologous protein and caspase-3 levels were determined using colorimetric methods. The oxidative stress, inflammation, endoplasmic reticulum stress and apoptosis levels increased statistically significantly in the IRI group compared with the sham operated group (p < 0.05). GA application improved these damage significantly (p < 0.05). Moreover, it was found that the results of histological examinations supported the biochemical results to a statistically significant extent. Our findings suggested that GA may be evaluated as a protective agent against testicular IRI.

Propolis ameliorates ischemia/reperfusion-induced testicular damage by reducing oxidative stress / El propóleo mejora el daño testicular inducido por isquemia/reperfusión al reducir el estrés oxidativo

Purpose: This study was performed to evaluate the effect of ethanolic extract of Turkish propolis (EEP) on testicular ischemia/reperfusion (I/R) damage in rats in terms of biochemistry and histopathology, for the first time. Methods: A total of 18 male Sprague-Dawley rats were divided into three groups with six rats in each group: control, torsion/detorsion (T/D), and T/D+EEP (100mg/kg). Testicular torsion was performed by 720° rotating the left testicle in a clockwise direction. The duration of ischemia was 4h and orchiectomy was performed after 2h of detorsion. EEP was applied only once 30min before detorsion. Tissue malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) levels were determined using colorimetric methods. Oxidative stress index (OSI) was calculated by proportioning tissue TOS and TAS values to each other. Tissue glutathione (GSH) and glutathione peroxidase (GPx) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. Johnsen's testicle scoring system was used for histological evaluation. Results: In the T/D group, it was determined that statistically significant decreasing in TAS, GSH, GPx levels and Johnsen score, and increasing in TOS, OSI and MDA levels (p<0.05) compared with control group. EEP administration statistically significantly restored this I/R damage (p<0.05). Conclusion: This is the first study to show that propolis prevent I/R-induced testicular damage through its antioxidant activity. More comprehensive studies are needed to see the underlying mechanisms. (AU)

Objetivo: Este estudio se realizó para evaluar por primera vez el efecto del extracto etanólico de propóleo turco (EEP) sobre el daño por isquemia/reperfusión (I/R) testicular en ratas en términos de bioquímica e histopatología. Métodos: Un total de 18 ratas macho Sprague-Dawley se dividieron en 3 grupos con 6 ratas en cada grupo: control, torsión/detorsión (T/D) y T/D+EEP (100mg/kg). La torsión testicular se realizó con una rotación de 720° del testículo izquierdo en el sentido de las agujas del reloj. La duración de la isquemia fue de 4h y la orquiectomía se realizó a las 2h de la detorsión. EEP se aplicó solo una vez 30min antes de la detorsión. Los niveles de malondialdehído tisular (MDA), estado oxidante total (TOS) y estado antioxidante total (TAS) se determinaron mediante métodos colorimétricos. El índice de estrés oxidativo (OSI) se calculó proporcionando los valores de TOS y TAS del tejido entre sí. Los niveles de glutatión tisular (GSH) y glutatión peroxidasa (GPx) se determinaron utilizando kits de ensayo inmunoabsorbente ligado a enzimas (ELISA). Se utilizó el sistema de puntuación de testículos de Johnsen para la evaluación histológica. Resultados: En el grupo T/D, se determina una disminución estadísticamente significativa en los niveles de TAS, GSH, GPx y puntuación de Johnsen y un aumento en los niveles de TOS, OSI y MDA (p<0,05) en comparación con el grupo control. La administración de EEP restauró de forma estadísticamente significativa este daño I/R (p<0,05). Conclusión: Este es el primer estudio que demuestra que el propóleo previene el daño testicular inducido por I/R a través de su actividad antioxidante. Se necesitan estudios más completos para ver los mecanismos subyacentes. (AU)

The ameliorative effect of Primula vulgaris on cisplatin-induced nephrotoxicity in rats and quantification of its phenolic components using LC-ESI-MS/MS.

Cisplatin (CDDP) is an important chemotherapeutic agent, accumulation of which in kidney tissue causes nephrotoxicity and renal failure. The aim of this study was to evaluate, for the first time in the literature, the protective effect of dimethyl sulfoxide (DMSO) extract of Primula vulgaris leaf (PVE) against CDDP-induced nephrotoxicity in rats. The PVE content was characterized using liquid chromatography-mass spectrometry. Nephrotoxicity was induced with a single dose of CDDP (7.5 mg/kg). Thirty female Wistar-Albino rats were divided into five groups (control, DMSO, CDDP (7.5 mg/kg), CDDP + PVE (25 mg/kg), and CDDP + PVE (50 mg/kg)). Biochemical and histopathological analyses were then performed. Rutin, gallic acid, p-coumaric acid and protocatechuic acid were identified as major components of PVE. Total antioxidant status and glutathione (GSH) values increased significantly in the serum samples from the treatment group compared to the CDDP group, while blood urea nitrogen, creatinine, oxidative stress index, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), total oxidant status, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) values decreased significantly. GSH levels increased significantly in the treatment group compared to the CDDP group, while TNF-α, caspase-3, 8-OHdG, MDA levels and damage scores decreased significantly. In conclusion, PVE exhibited strong protective effects through its anti-apoptotic, antioxidant, and anti-inflammatory activities against nephrotoxicity and oxidative damage caused by CDDP in rats.

Propolis ameliorates ischemia/reperfusion-induced testicular damage by reducing oxidative stress.

PURPOSE: This study was performed to evaluate the effect of ethanolic extract of Turkish propolis (EEP) on testicular ischemia/reperfusion (I/R) damage in rats in terms of biochemistry and histopathology, for the first time. METHODS: A total of 18 male Sprague-Dawley rats were divided into three groups with six rats in each group: control, torsion/detorsion (T/D), and T/D+EEP (100mg/kg). Testicular torsion was performed by 720° rotating the left testicle in a clockwise direction. The duration of ischemia was 4h and orchiectomy was performed after 2h of detorsion. EEP was applied only once 30min before detorsion. Tissue malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) levels were determined using colorimetric methods. Oxidative stress index (OSI) was calculated by proportioning tissue TOS and TAS values to each other. Tissue glutathione (GSH) and glutathione peroxidase (GPx) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. Johnsen's testicle scoring system was used for histological evaluation. RESULTS: In the T/D group, it was determined that statistically significant decreasing in TAS, GSH, GPx levels and Johnsen score, and increasing in TOS, OSI and MDA levels (p<0.05) compared with control group. EEP administration statistically significantly restored this I/R damage (p<0.05). CONCLUSION: This is the first study to show that propolis prevent I/R-induced testicular damage through its antioxidant activity. More comprehensive studies are needed to see the underlying mechanisms.

Chlorogenic acid ameliorates torsion/detorsion-induced testicular injury via decreasing endoplasmic reticulum stress.

BACKROUND: Testicular torsion (TT) is an urological emergency situation especially in adolescents and young men. The main pathophysiology of testicular torsion/detorsion (T/D) is ischemia-reperfusion (I/R) injury. I/R induces the production of reactive oxygen species (ROS) thought to play a critical role in tissue injury. Increasing evidence suggests that ER stress may play an important role in I/R-induced cell death. During ischemia, oxygen and glucose deprivation also causes abnormalities in protein folding processes. Antioxidants suppress oxidative stress directly as well as ER stress and thus gain importance in the treatment of pathologies associated with oxidative stress and ER stress, such as I/R damage. Chlorogenic acid (CGA) which is formed by the esterification of caffeic and quinic acids and is one of the most abundant phenolic acids in nature. There is also a growing body of studies reporting protective effects of CGA against I/R injury in different tissues, including intestinal, heart and brain. OBJECTIVE: To investigate the effects of CGA on oxidative stress and ER stress in an experimental testicular I/R injury model. DESIGN: Rats were divided into three groups: control, T/D, and T/D + CGA. In the T/D + CGA group, 100 mg/kg CGA was given intraperitoneally 30 min before detorsion. While tissue malondialdehyde (MDA) levels were determined manually using a colorimetric method, tissue superoxide dismutase (SOD), 78-kDa glucose regulatory protein (GRP78), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP) levels were determined enzyme-linked immunosorbent assay (ELISA) kits. Johnsen's testicle scoring system was used for histological evaluation. RESULTS: In T/D group, tissue MDA, GRP78, ATF6 and CHOP levels were significantly higher than control group (p < 0.05). These increases were significantly reversed with CGA pre-treatment (p < 0.05). The histopathological Johnsen score was significantly lower in the T/D group compared to the control group, but the level of histopathological Johnsen score was significantly restored by CGA pre-treatment (p < 0.05). DISCUSSION: The relationship between I/R injury and ER stress has been emphasized frequently in recent years. This study in which the effects of CGA on TT were examined for the first time, showed that CGA can inhibit I/R-induced testicular damage. CONCLUSION: These results may provide a new insight into CGA and may form the first clinical theoretical basis for the possible use of CGA in the treatment of TT in the future. However, the real function of CGA in TT patients needs further investigation.

Astaxanthin Protects Testicular Tissue against Torsion/Detorsion-Induced Injury via Suppressing Endoplasmic Reticulum Stress in Rats.

BACKGROUND: The aim of this study was to investigate the effects of astaxanthin (ASX) on testicular torsion/detorsion (T/D) damage in rats in terms of oxidative stress and endoplasmic reticulum (ER) stress. METHODS: Eighteen male Sprague-Dawley rats were divided into three groups with six rats in each group: control, T/D and T/D + 20 mg/kg ASX. Torsion and detorsion times were applied as 4 h and 2 h, respectively. ASX application was performed 30 minutes before detorsion. At the end of the period, testicular tissues were removed and biochemical and histological analyzes were performed. To evaluate the degree of oxidative stress, tissue malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) were determined using colorimetric methods, while tissue superoxide dismutase (SOD) levels were determined using ELISA kit. To evaluate the degree of ER stress, tissue glucose regulatory protein 78 (GRP78), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP) levels were determined using ELISA kits. Johnsen's testicle scoring system was used for histological evaluation. RESULTS: In the T/D group, it is determined that statistically significant decreasing in TAS, SOD levels and Johnsen score, and increasing in TOS, OSI, MDA, GRP78, ATF6 and CHOP levels (p < 0.001) compared with control group. ASX administration statistically significantly restored this T/D-induced damage (p < 0.01). CONCLUSION: This is the first study to show that ASX prevent T/D-induced testicular damage through its antioxidant activity. More comprehensive studies are needed to see the underlying mechanisms.

Effect of Chrysin on Endoplasmic Reticulum Stress in a Rat Model of Testicular Torsion.

BACKGROUND: The purpose of this study was to evaluate the possible therapeutic effect of chrysin (CHS) on testicular torsion/detorsion (T/D) injury in vivo through the mechanisms of oxidative stress and endoplasmic reticulum stress (ERS). METHODS: Eighteen male rats were divided into three groups of six subjects in each group: control, T/D and T/D + CHS (100 mg/kg). To evaluate the degree of oxidative stress, tissue malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) levels were determined using colorimetric methods, while tissue superoxide dismutase (SOD) levels were determined using an ELISA kit. To evaluate the degree of ERS, tissue glucose regulatory protein 78 (GRP78), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP) levels were determined using ELISA kits. Johnsen's testicle scoring system was used for histological evaluation. RESULTS: In the T/D group, it is determined that statistically significant decreasing in the levels of TAS, SOD and Johnsen score, and increasing in TOS, MDA, GRP78, ATF6 and CHOP levels compared to control group (p < 0.05). CHS administration statistically significantly restored this T/D-induced damage (p < 0.05). CONCLUSION: This is the first study to show that CHS prevent T/D-induced testicular damage through its ERS inhibitor activity. More comprehensive studies are needed to understand the underlying mechanisms.Supplemental data for this article is available online at https://doi.org/10.1080/08941939.2021.2015489 .

Prognostic factors for 30-days mortality in eighty years aged and older critically ill patients: a single center retrospective cohort study

Background/aim: Nowadays, with the rise in average life expectancy, the rate of hospitalization of the older population in intensive care unit (ICU) is gradually increasing. Unfortunately, there are no ideal combination of prognostic factors predicting the mortality in older patients admitted to the ICU. In the present study, we aim to determine the prognostic factors and their impacts on short-time mortality in older critically ill patients. Materials and methods: This retrospective cohort study was performed between January 2019 and February 2020. We included 133 patients aged ≥80 years and hospitalized ≥24 h in the ICU. Results: A total of 133 critically ill patients enrolled in the present study. And, the median age of the patients was 85 (80­106) years. 30-days and overall ICU mortality rates were found 30.1% and 34.6%, respectively. The patients were grouped as survivors (n = 94) and nonsurvivors (n = 39). Hospital length of stay before the ICU admission was found significantly longer in nonsurvivors (p = 0.001). Sequential organ failure assessment (SOFA) score and acute physiology and chronic health evaluation-II (APACHE-II) score were significantly higher in nonsurvivors (p < 0.001, p < 0.001). Also, blood lactate level and glucose level were respectively significantly higher in nonsurvivors (p < 0.001, p = 0.006). We found that modified nutrition risk in critically ill (mNUTRIC) score and prehospital clinical frailty scale (CFS) were independent prognostic factors for the older critically ill patients (HR = 9.19, 95% CI=1.47­57.32, p = 0.018, HR = 20.16, 95% CI = 2.63­54.07, p =0.004). Conclusion: mNUTRIC score and prehospital CFS score were the most important prognostic factors in the admission of older patients to intensive care units.

Primary renal angiosarcoma: A case report and a short review of literature.

Primary renal angiosarcomas (AS) are uncommon tumors with poor prognosis. Aetiology is unknown but some unproven risk factors have been described. It is difficult to discriminate these masses from renal cell carcinomas or other renal masses with imaging modalities. Immunohistochemistry plays an important role in the diagnosis. Main treatment protocol for primary renal AS is still controversial and nephrectomy with chemotherapy and/or radiotherapy seems the only treatment option. We state a primary renal angiosarcoma case for its rareness and contribution to literature.

Berberine inhibits the ischemia-reperfusion induced testicular injury through decreasing oxidative stress.

PURPOSE: The aim of this study was to investigate the effect of berberine (BBR) on oxidative stress in an experimental testicular I/R injury model. METHODS: Eighteen rats were divided into three groups: control group, torsion-detorsion (T/D) group, and BBR + T/D group. In the pre-treatment of the BBR group, 200 mg/kg BBR was given intraperitoneally 30 min before detorsion. Tissue malondialdehyde (MDA), total oxidant status (TOS), and total antioxidant status (TAS) levels were determined using colorimetric methods. Histological evaluation of the tissue samples was evaluated using hematoxylin-eosin staining. RESULTS: In T/D group, tissue MDA, TOS, and oxidative stress index levels were higher than control group. These increases were significantly reversed with BBR pre-treatment. Although Johnsen scores were lower in T/D group than the control group, BBR pre-treatment recovered the Johnsen scores. CONCLUSION: These results suggest that BBR can inhibit I/R-induced testicular injury by suppressing oxidative stress. Further studies may prove that BBR is a useful agent as an adjunctive treatment in surgical repair in human cases.

Comparison of hemodynamic responses and QTc intervals to tracheal intubation with the McGRATH MAC videolaryngoscope and the Macintosh direct laryngoscope in elderly patients.

Our hypothesis was that intubations with the McGRATH MAC videolaryngoscope in elderly patients would produce less hemodynamic responses and ECG changes than the Macintosh direct laryngoscope. The patients were divided into two groups: patients who were intubated using the McGRATH MAC (Group V, n = 45) and patients who were intubated using the Macintosh direct laryngoscope (Group L, n = 45). Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), heart rate (HR) were recorded before induction with anesthesia (baseline), immediately after induction and at 1 min, 3 min, and 5 min after intubation, with simultaneous ECG. When Group L was compared to Group V, there was an increase in the first, third and fitth minutes after intubation in terms of HR. SBP, MAP increased only at 1 min after intubation and DBP increased in the first and third minutes after intubation in Group L. In Group L, there was a significant difference in the HR values immediately after induction and the first minute after intubation compared with the baseline values. There was a difference in the SBP values immediately after induction and at 3 min and 5 min after intubation compared with the baseline values. There was a difference in DBP and MAP values immediately after induction and at 5 min after intubation. When the McGRATH MAC videolaryngoscope was compared with the Macintosh direct laryngoscope in elderly patients, the McGRATH MAC videolaryngoscope decreased the hemodynamic fluctuations due to tracheal intubation.

The possible protective effects of dipyridamole on ischemic reperfusion injury of priapism.

PURPOSE: To investigate the protective effects against ischemia reperfusion injury of dipyridamole in a model of induced priapism in rats. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley rats were divided into four groups, control, P/R, P/R+DMSO and P/R+D. 3ml blood specimens were collected from vena cava inferior in order to determine serum MDA, IMA, TAS, TOS and OSI values, and penile tissue was taken for histopathological examination in control group. Priapism was induced in P/R group. After 1h, priapism was concluded and 30 min reperfusion was performed. In P/R+DMSO group 1ml/kg DMSO was administered intraperitoneally 30 min before reperfusion, while in P/R+D group 10mg/kg dipyridamole was administered intraperitoneally 30 min before reperfusion. Blood and penis specimens were collected after the end of 30 min reperfusion period. Sinusoidal area (µm2), tears in tunica albuginea and injury parameters in sinusoidal endothelium of penis were investigated. RESULTS: Histopathological examination revealed no significant changes in term of sinusoidal area. A decrease in tears was observed in P/R+D group compared to P/R group (p<0.05). Endothelial injury decreased in P/R+D group compared to P/R group (p>0.05). There were no significant differences in MDA and IMA values between groups. A significant increase in TOS and OSI values was observed in P/R+D group compared to P/R group. A significant decrease in TAS levels was observed in P/R+D group compared to the P/R group. CONCLUSIONS: The administration of dipyridamole before reperfusion in ischemic priapism model has a potential protective effect against histopathological injury of the penis.

The possible protective effects of dipyridamole on ischemic reperfusion injury of priapism

ABSTRACT Purpose To investigate the protective effects against ischemia reperfusion injury of dipyridamole in a model of induced priapism in rats. Materials and Methods Twenty-four male Sprague-Dawley rats were divided into four groups, control, P/R, P/R+DMSO and P/R+D. 3ml blood specimens were collected from vena cava inferior in order to determine serum MDA, IMA, TAS, TOS and OSI values, and penile tissue was taken for histopathological examination in control group. Priapism was induced in P/R group. After 1h, priapism was concluded and 30 min reperfusion was performed. In P/R+DMSO group 1ml/kg DMSO was administered intraperitoneally 30 min before reperfusion, while in P/R+D group 10mg/kg dipyridamole was administered intraperitoneally 30 min before reperfusion. Blood and penis specimens were collected after the end of 30 min reperfusion period. Sinusoidal area (µm2), tears in tunica albuginea and injury parameters in sinusoidal endothelium of penis were investigated. Results Histopathological examination revealed no significant changes in term of sinusoidal area. A decrease in tears was observed in P/R+D group compared to P/R group (p<0.05). Endothelial injury decreased in P/R+D group compared to P/R group (p>0.05). There were no significant differences in MDA and IMA values between groups. A significant increase in TOS and OSI values was observed in P/R+D group compared to P/R group. A significant decrease in TAS levels was observed in P/R+D group compared to the P/R group. Conclusions The administration of dipyridamole before reperfusion in ischemic priapism model has a potential protective effect against histopathological injury of the penis.

Postcircumcisional ischemia of the glans penis treated with pentoxifylline.

Ischemia of the glans penis is a rare postcircumcision complication. We describe a four-year-old boy developing ischemia of the glans penis 48 h after circumcision. The ischemia completely resolved following treatment with iv pentoxifylline (PTX) for six days, and the patient was discharged without any problems. PTX treatment should be kept in mind as an alternative treatment modality in ischemia of the glans penis which is a serious potential post-circumcision complication.